December 2013
1295
arylisoxazol-4′-ylsulfonyl)methyl)-1,3,4-oxadiazole (5a–c) phenyl-1′H-pyrazol-4′-ylsulfonyl)ꢀmethyl)-1,3,4-oxadiazoleꢀ
A mixture of compound 3 (1mmol), benzaldoxime (1.2mmol), (6a):ꢀWhiteꢀsolid,ꢀyieldꢀ62%,ꢀmpꢀ180–182°C.ꢀIRꢀ(KBr)ꢀcm−1:ꢀ
chloramine-Tꢀ (1.2ꢀmmol)ꢀ andꢀ methanolꢀ (20ꢀmL)ꢀ wasꢀ refluxedꢀ 1125, 1329 (SO2), 1562 (C=N), 1627 (C=C), 3260 (NH).
forꢀ14–17ꢀh.ꢀTheꢀprecipitatedꢀinorganicꢀsaltsꢀwereꢀfilteredꢀoff.ꢀ 1H-NMRꢀ (DMSO-d6) δ:ꢀ 5.09ꢀ (s,ꢀ 2H,ꢀ CH2-(C-5)),ꢀ 5.30ꢀ (s,ꢀ 2H,ꢀ
Theꢀ filtrateꢀ wasꢀ concentratedꢀ andꢀ theꢀ residueꢀ wasꢀ extractedꢀ CH2-(C-2)),ꢀ 7.06–7.71ꢀ (m,ꢀ 20H,ꢀ Ar-H),ꢀ 10.55ꢀ (brꢀs,ꢀ 1H,ꢀ NH).ꢀ
with dichloromethane. The organic layer was washed with 13C-NMRꢀ (DMSO-d6) δ:ꢀ 45.6ꢀ (CH2-(C-5)),ꢀ 50.2ꢀ (CH2-(C-2)),ꢀ
water, brine and dried (an. Na2SO4).ꢀ Evaporationꢀ ofꢀ theꢀ sol- 136.9ꢀ (C-4′),ꢀ 146.2ꢀ (C-3′),ꢀ 149.7ꢀ (C-5′),ꢀ 157.5ꢀ (C-5),ꢀ 158.3ꢀ
vent under reduced pressure yielded a solid which was puri- (C-2),ꢀ 123.3,ꢀ 123.6,ꢀ 124.1,ꢀ 124.9,ꢀ 126.6,ꢀ 127.4,ꢀ 128.2,ꢀ 129.5,ꢀ
fiedꢀ byꢀ columnꢀ chromatographyꢀ (silicaꢀ gel,ꢀ 60–120ꢀ mesh)ꢀ 130.1, 131.7, 132.4, 133.5 (aromatic carbons). MS m/z:ꢀ 611.70ꢀ
usingꢀhexane–ethylꢀacetateꢀ(4ꢀ:ꢀ1)ꢀasꢀeluent.
2-((Phenylaminosulfonyl)ꢀmethyl)-5-((4′,5′-dihydro-3′- 11.45.ꢀFound:ꢀC,ꢀ61.25;ꢀH,ꢀ4.31;ꢀN,ꢀ11.69.
(M+). Anal. Calcd for C31H25N5O5S2:ꢀ C,ꢀ 60.86;ꢀ H,ꢀ 4.12;ꢀ N,ꢀ
phenyl-5′-phenylisoxazol-4′-ylsulfonyl)mꢀ ethyl)-1,3,4-
2-(( p-Methylphenylaminosulfonyl)ꢀmethyl)-5-((1′,3′-
oxadiazoles (5a):ꢀ Whiteꢀ solid,ꢀ yieldꢀ 67%,ꢀ mpꢀ 149–151°C.ꢀ diphenyl-5′-(p-methylphenyl)-1′H-pyrazol-4′-ylsulfonyl)-
IR (KBr) cm−1:ꢀ 1140,ꢀ 1330ꢀ (SO2), 1560 (C=N), 3237 (NH). methyl)-1,3,4-oxadiazoleꢀ (6b):ꢀ Whiteꢀ solid,ꢀ yieldꢀ 66%,ꢀ mpꢀ
1H-NMRꢀ (DMSO-d6) δ:ꢀ 4.89ꢀ (s,ꢀ 2H,ꢀ CH2-(C-5)),ꢀ 5.18ꢀ (d,ꢀ 1H,ꢀ 168–170°C. IR (KBr) cm−1:ꢀ 1130,ꢀ 1335ꢀ (SO2), 1570 (C=N),
1
C4′-H,ꢀ J=7.6Hz), 5.20 (s, 2H, CH2-(C-2)),ꢀ 5.43ꢀ (d,ꢀ 1H,ꢀ C5′-H,ꢀ 1624 (C=C), 3265 (NH). H-NMRꢀ (DMSO-d6) δ:ꢀ 2.26ꢀ andꢀ
J=7.6ꢀHz),ꢀ 7.31–7.85ꢀ (m,ꢀ 15H,ꢀ Ar-H),ꢀ 10.50ꢀ (brꢀs,ꢀ 1H,ꢀ NH).ꢀ 2.39ꢀ (s,ꢀ 6H,ꢀ Ar-CH3), 5.03 (s, 2H, CH2-(C-5)),ꢀ 5.28ꢀ (s,ꢀ 2H,ꢀ
13C-NMRꢀ (DMSO-d6) δ:ꢀ 48.6ꢀ (CH2-(C-5)),ꢀ 53.4ꢀ (CH2-(C-2)),ꢀ CH2-(C-2)),ꢀ 6.94–7.52ꢀ (m,ꢀ 18H,ꢀ Ar-H),ꢀ 10.50ꢀ (brꢀs,ꢀ 1H,ꢀ NH).ꢀ
64.5ꢀ (C-4′),ꢀ85.3ꢀ(C-5′),ꢀ155.2ꢀ(C-3′),ꢀ158.1ꢀ(C-5),ꢀ158.9ꢀ(C-2),ꢀ 13C-NMRꢀ (DMSO-d6) δ:ꢀ 21.5ꢀ andꢀ 22.4ꢀ (Ar-CH3), 45.8 (CH2-
125.7, 126.1, 127.3, 129.5, 130.6, 131.4, 132.1, 135.7 (aromatic (C-5)),ꢀ 49.9ꢀ (CH2-(C-2)),ꢀ 136.3ꢀ (C-4′),ꢀ 145.9ꢀ (C-3′), 148.7
carbons). MS m/z:ꢀ538.64ꢀ(M+). Anal. Calcd for C25H22N4O6S2:ꢀ (C-5′),ꢀ 156.6ꢀ (C-5),ꢀ 157.6ꢀ (C-2),ꢀ 122.7,ꢀ 123.1,ꢀ 123.9,ꢀ 124.8,ꢀ
C,ꢀ55.74;ꢀH,ꢀ4.11;ꢀN,ꢀ10.40.ꢀFound:ꢀC,ꢀ56.03;ꢀH,ꢀ4.29;ꢀN,ꢀ10.47. 124.9, 126.8, 127.5, 128.6, 129.7, 130.3, 131.6, 134.1 (aromatic
2-(( p-Methylphenylaminosulfonyl)ꢀmethyl)-5-((4′,5′- carbons). MS m/z:ꢀ639.76ꢀ(M+). Anal. Calcd for C33H29N5O5S2:ꢀ
dihydro-3′-phenyl-5′-(p-methylphenyl)ꢀisoxazol-4′-ylsulfonyl)- C,ꢀ61.95;ꢀH,ꢀ4.56;ꢀN,ꢀ10.94.ꢀFound:ꢀC,ꢀ62.28;ꢀH,ꢀ4.93;ꢀN,ꢀ11.13.
methyl)-1,3,4-oxadiazolesꢀ (5b):ꢀ Whiteꢀ solid,ꢀ yieldꢀ 60%,ꢀ mpꢀ
2-(( p-Chlorophenylaminosulfonyl)ꢀmethyl)-5-((1′,3′-
129–131°C. IR (KBr) cm−1:ꢀ 1134,ꢀ 1324ꢀ (SO2), 1555 (C= diphenyl-5′-(p-chlorophenyl)-1′H-pyrazol-4'-ylsulfonyl)-
N), 3230 (NH). 1H-NMRꢀ (DMSO-d6) δ:ꢀ 2.28ꢀ andꢀ 2.42ꢀ (s,ꢀ methyl)-1,3,4-oxadiazoleꢀ (6c):ꢀ Whiteꢀ solid,ꢀ yieldꢀ 69%,ꢀ mpꢀ
6H,ꢀ Ar-CH3), 4.94 (s, 2H, CH2-(C-5)),ꢀ 5.12ꢀ (d,ꢀ 1H,ꢀ C4′-H,ꢀ 188–190°C. IR (KBr) cm−1:ꢀ 1137,ꢀ 1338ꢀ (SO2), 1575 (C=N),
J=7.2Hz), 5.14 (s, 2H, CH2-(C-2)),ꢀ 5.36ꢀ (d,ꢀ 1H,ꢀ C5′-H,ꢀ 1632 (C=C), 3272 (NH). 1H-NMRꢀ (DMSO-d6) δ:ꢀ 5.16ꢀ (s,ꢀ
J=7.2ꢀHz),ꢀ 7.21–7.72ꢀ (m,ꢀ 13H,ꢀ Ar-H),ꢀ 10.49ꢀ (brꢀs,ꢀ 1H,ꢀ NH).ꢀ 2H, CH2-(C-5)),ꢀ 5.39ꢀ (s,ꢀ 2H,ꢀ CH2-(C-2)),ꢀ 7.14–7.91ꢀ (m,ꢀ 18H,ꢀ
13C-NMRꢀ (DMSO-d6) δ:ꢀ 22.6ꢀ andꢀ 24.2ꢀ (Ar-CH3), 47.5 (CH2- Ar-H),ꢀ 10.64ꢀ (brꢀs,ꢀ 1H,ꢀ NH).ꢀ 13C-NMRꢀ (DMSO-d6) δ:ꢀ 46.8ꢀ
(C-5)),ꢀ 52.1ꢀ (CH2-(C-2)),ꢀ 62.9ꢀ (C-4′),ꢀ84.2ꢀ(C-5′),ꢀ153.3ꢀ(C-3′), (CH2-(C-5)),ꢀ 52.2ꢀ (CH2-(C-2)),ꢀ 137.5ꢀ (C-4′),ꢀ 147.3ꢀ (C-3′),
157.4ꢀ (C-5),ꢀ 158.1ꢀ (C-2),ꢀ 124.5,ꢀ 125.2,ꢀ 127.6,ꢀ 128.4ꢀ 129.3,ꢀ 150.2ꢀ (C-5′),ꢀ 157.5ꢀ (C-5),ꢀ 158.9ꢀ (C-2),ꢀ 124.3,ꢀ 124.6,ꢀ 125.9,ꢀ
130.6, 133.2, 134.8 (aromatic carbons). MS m/z:ꢀ 566.67ꢀ (M+). 126.3, 127.6, 128.5, 129.8, 130.5, 131.6, 132.3, 133.6, 134.7
Anal. Calcd for C27H26N4O6S2:ꢀ C,ꢀ 57.22;ꢀ H,ꢀ 4.62;ꢀ N,ꢀ 9.88.ꢀ (aromatic carbons). MS m/z:ꢀ 680.59ꢀ (M+). Anal. Calcd for
Found:ꢀC,ꢀ57.34;ꢀH,ꢀ4.90;ꢀN,ꢀ10.01.
C31H23Cl2N5O5S2:ꢀC,ꢀ54.70;ꢀH,ꢀ3.40;ꢀN,ꢀ10.28.ꢀFound:ꢀC,ꢀ54.79;ꢀ
2-(( p-Chlorophenylaminosulfonyl)ꢀmethyl)-5-((4′,5′- H, 3.65; N, 10.34.
dihydro-3′-phenyl-5′-(p-chlorophenyl)ꢀisoxazol-4′-ylsulfonyl)-
2-((Phenylaminosulfonyl)mꢀ ethyl)-5-((3′-phenyl-5′-
methyl)-1,3,4-oxadiazolesꢀ (5c):ꢀ Whiteꢀ solid,ꢀ yieldꢀ 73%,ꢀ mpꢀ phenylisoxazol-4′-ylsulfonyl)ꢀmethyl)-1,3,4-oxadiazoleꢀ
(7a):ꢀ
171–173°C. IR (KBr) cm−1:ꢀ 1146,ꢀ 1333ꢀ (SO2), 1564 (C=N), Whiteꢀsolid,ꢀyieldꢀ71%,ꢀmpꢀ153–155°C.ꢀIRꢀ(KBr)ꢀcm−1:ꢀ1120,ꢀ
1
1
3245 (NH). H-NMRꢀ (DMSO-d6) δ:ꢀ 4.99ꢀ (s,ꢀ 2H,ꢀ CH2-(C-5)),ꢀ 1323 (SO2), 1580 (C=N), 1620 (C=C), 3268 (NH). H-NMRꢀ
5.23 (d, 1H, C4′-H,ꢀJ=7.7Hz), 5.27 (s, 2H, CH2-(C-2)),ꢀ5.51ꢀ(d,ꢀ (DMSO-d6) δ:ꢀ5.26ꢀ(s,ꢀ2H,ꢀCH2-(C-5)),ꢀ5.41ꢀ(s,ꢀ2H,ꢀCH2-(C-2)),ꢀ
1H, C5′-H,ꢀ J=7.7ꢀHz),ꢀ 7.38–7.93ꢀ (m,ꢀ 13H,ꢀ Ar-H),ꢀ 10.59ꢀ (brꢀs,ꢀ 7.19–7.84ꢀ (m,ꢀ 15H,ꢀ Ar-H),ꢀ 10.57ꢀ (brꢀs,ꢀ 1H,ꢀ NH).ꢀ 13C-NMRꢀ
1H, NH). 13C-NMRꢀ (DMSO-d6) δ:ꢀ 49.5ꢀ (CH2-(C-5)),ꢀ 53.8ꢀ (DMSO-d6) δ:ꢀ47.1ꢀ(CH2-(C-5)),ꢀ51.5ꢀ(CH2-(C-2)),ꢀ138.2ꢀ(C-4′),
(CH2-(C-2)),ꢀ 61.4ꢀ (C-4′),ꢀ83.7ꢀ(C-5′),ꢀ152.8ꢀ(C-3′),ꢀ158.8ꢀ(C-5),ꢀ 147.3ꢀ(C-3′),ꢀ151.4ꢀ(C-5′),ꢀ157.9ꢀ(C-5),ꢀ158.5ꢀ(C-2),ꢀ125.1,ꢀ126.6,ꢀ
159.2ꢀ (C-2),ꢀ 123.7,ꢀ 125.8,ꢀ 126.9,ꢀ 127.5,ꢀ 128.8,ꢀ 130.1,ꢀ 131.9,ꢀ 127.1, 128.4, 129.2, 130.4, 131.8, 133.5 (aromatic carbons). MS
136.6 (aromatic carbons). MS m/z:ꢀ 607.51ꢀ (M+). Anal. Calcd m/z:ꢀ536.60ꢀ(M+). Anal. Calcd for C25H20N4O6S2:ꢀC,ꢀ55.95;ꢀH,ꢀ
for C25H20Cl2N4O6S2:ꢀ C,ꢀ 49.42;ꢀ H,ꢀ 3.31;ꢀ N,ꢀ 9.22.ꢀ Found:ꢀ C,ꢀ 3.75;ꢀN,ꢀ10.44.ꢀFound:ꢀC,ꢀ56.07;ꢀH,ꢀ3.84;ꢀN,ꢀ10.71.
49.15; H, 3.37; N, 9.08.
2-((p-Methylphenylaminosulfonyl)ꢀmethyl)-5-((3′-phenyl-5′-
General Procedure for the Synthesis of 2-((Aryl- ( p-methylphenyl)ꢀisoxazol-4′-ylsulfonyl)ꢀmethyl)-1,3,4-
aminosulfonyl)methyl)-5-((1′,3′-diphenyl-5′-aryl-1′H- oxadiazole (7b):ꢀ Whiteꢀ solid,ꢀ yieldꢀ 68%,ꢀ mpꢀ 141–143°C.ꢀ IRꢀ
pyrazol-4′-ylsulfonyl)methyl)-1,3,4-oxadiazole
(6a–c)/2- (KBr) cm−1:ꢀ1115,ꢀ1325ꢀ(SO2), 1583 (C=N), 1618 (C=C), 3264
1
((Arylaminosulfonyl)methyl)-5-((3′-phenyl-5′-aryl- (NH). H-NMRꢀ(DMSO-d6) δ:ꢀ2.30ꢀandꢀ2.45ꢀ(s,ꢀ6H,ꢀAr-CH3),
isoxazol-4′-ylsulfonyl)methyl)-1,3,4-oxadiazoles(7a–c) The 5.21 (s, 2H, CH2-(C-5)),ꢀ5.32ꢀ(s,ꢀ2H,ꢀCH2-(C-2)),ꢀ7.24–7.88ꢀ(m,ꢀ
compound 4/5 (1mmol), chloranil (1.2mmol) in xylene (10mL) 13H,ꢀ Ar-H),ꢀ 10.60ꢀ (brꢀs,ꢀ 1H,ꢀ NH).ꢀ 13C-NMRꢀ (DMSO-d6) δ:ꢀ
wasꢀrefluxedꢀforꢀ23–26ꢀh.ꢀThen,ꢀitꢀwasꢀtreatedꢀwithꢀ5%ꢀsodiumꢀ 22.4ꢀ andꢀ 23.1ꢀ (Ar-CH3), 46.4 (CH2-(C-5)),ꢀ 51.1ꢀ (CH2-(C-2)),ꢀ
hydroxide solution. The organic extract was separated, washed 137.5ꢀ (C-4′),ꢀ 146.5ꢀ (C-3′),ꢀ 150.4ꢀ (C-5′),ꢀ 157.2ꢀ (C-5),ꢀ 158.1ꢀ
with water and dried (an. Na2SO4). The solvent was removed (C-2),ꢀ 124.5,ꢀ 125.7,ꢀ 126.4,ꢀ 127.8,ꢀ 128.7,ꢀ 129.7,ꢀ 130.6,ꢀ 132.9ꢀ
under reduced pressure. The resultant solid was recrystallized (aromatic carbons). MS m/z:ꢀ 564.65ꢀ (M+). Anal. Calcd for
fromꢀ2-propanol.
C27H24N4O6S2:ꢀC,ꢀ57.43;ꢀH,ꢀ4.28;ꢀN,ꢀ9.92.ꢀFound:ꢀC,ꢀ57.38;ꢀH,ꢀ
2-((Phenylaminosulfonyl)ꢀmethyl)-5-((1′,3′-diphenyl-5′- 4.61; N, 9.74.